The project objective continues to be devoted to (1) studying the pharmacologic actions as well as some of the biochemical and biophysical mechanisms of action of catecholamines and neurohypophyseal polypeptide hormones on micro- and macro-vascular smooth muscle, (2) determining whether the natural catecholamines and neurohypophyseal polypeptide hormones and some of their synthetic analogues exert selective vasotropic effects on specific types of muscular microvessels initially in the in-vivo rat micro-circulation, and (3) having documented the foregoing as a frame of reference some of the same drugs will be examined for their pharmacodynamic actions and structure-activity relationships on micro- and macro-vascular muscle both in-vivo and in-vitro in different vascular beds of different laboratory species of animals as well as human blood vessels. As the peripheral site(s) of action(s) of the synthetic molecules are determined in the various regional microcirculatory beds, some are being selected for trial as therapeutic agents in the treatment of experimental shock; the latter to serve as a potential source of new drugs for clinical application.